BACKGROUND: Assessing the relative value of cocaine and how it changes with
chronic drug use represents a long-standing goal in addiction research.
Surprisingly, recent experiments in rats–by far the most frequently used animal
model in this field–suggest that the value of cocaine is lower than previously
thought.
METHODOLOGY/PRINCIPAL FINDINGS: Here we report a series of choice experiments
that better define the relative position of cocaine on the value ladder of rats
(i.e., preference rank-ordering of different rewards). Rats were allowed to
choose either taking cocaine or drinking water sweetened with saccharin–a
nondrug alternative that is not biologically essential. By systematically varying
the cost and concentration of sweet water, we found that cocaine is low on the
value ladder of the large majority of rats, near the lowest concentrations of
sweet water. In addition, a retrospective analysis of all experiments over the
past 5 years revealed that no matter how heavy was past cocaine use most rats
readily give up cocaine use in favor of the nondrug alternative. Only a minority,
fewer than 15% at the heaviest level of past cocaine use, continued to take
cocaine, even when hungry and offered a natural sugar that could relieve their
need of calories.
CONCLUSIONS/SIGNIFICANCE: This pattern of results (cocaine abstinence in most
rats; cocaine preference in few rats) maps well onto the epidemiology of human
cocaine addiction and suggests that only a minority of rats would be vulnerable
to cocaine addiction while the large majority would be resilient despite
extensive drug use. Resilience to drug addiction has long been suspected in
humans but could not be firmly established, mostly because it is difficult to
control retrospectively for differences in drug self-exposure and/or availability
in human drug users. This conclusion has important implications for preclinical
research on the neurobiology of cocaine addiction and for future medication
development.